醋酸亮丙瑞林犬体内样品分析方法建立及动力学行为比较  

Establishment of analytical method and comparison of kinetic behavior of leuprolide acetate in dogs

作　　者：姜兴颖 金艺[1] 杨楠 赵莹莹 徐海燕[1] 袁波[1] JIANG Xingying;JIN Yi;YANG Nan;ZHAO Yingying;XU Haiyan;YUAN Bo(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2021年第6期559-566,595,共9页Journal of Shenyang Pharmaceutical University

摘　　要：目的通过LC-MS/MS法测定犬血清中亮丙瑞林浓度,比较3.75 mg与11.25 mg醋酸亮丙瑞林缓释微球在Beagle犬体内释放行为。方法16只Beagle犬分别在禁食12 h后皮下注射醋酸亮丙瑞林缓释微球3.75 mg与11.25 mg制剂,血清样品经蛋白沉淀法处理后采用LC-MS/MS法进行检测,使用WinNonlin 6.4计算主要动力学参数,使用SPSS软件对主要动力学参数进行统计分析。结果犬血清中亮丙瑞林的质量浓度在0.0781~50.0μg·L^(-1)范围内线性关系良好;皮下注射醋酸亮丙瑞林缓释微球3.75 mg与11.25 mg制剂后的主要动力学数据为:ρ_(max)分别为(6.01±1.37)μg·L^(-1)及(75.50±11.65)μg·L^(-1),tmax分别为(0.84±0.13)h及(1.31±0.59)h,t_(1/2)分别为(242.62±164.59)h及(388.64±135.75)h,AUC_(0-t)分别为(104.26±46.57)μg·h·L^(-1)及(640.57±180.92)μg·h·L^(-1),AUC_(0-∞)分别为(152.18±79.72)μg·h·L^(-1)及(701.21±178.01)μg·h·L^(-1)。对两组的主要药动学参数采用独立样本t检验进行统计分析,t max、t_(1/2)、AUC_(0-t)及AUC_(0-∞)无显著性差异(P>0.05),ρ_(max)具有显著性差异(P<0.05)。结论经给药剂量校正后,3.75 mg制剂的ρ_(max)明显低于11.25 mg制剂,3.75 mg制剂相较于11.25 mg制剂具有较低的突释;11.25 mg制剂与3.75 mg制剂AUC无显著性差异。Objective To compare the release behavior of 3.75 mg and 11.25 mg of leuprolide acetate sustained-release microspheres in Beagle dogs by LC-MS/MS.Methods 16 Beagle dogs were subcutaneously injected with 3.75 mg and 11.25 mg of leuprolide acetate sustained-release microspheres after fasting for 12 h.The Serum samples were processed by protein precipitation method and detected by LC-MS/MS.The main pharmacokinetic parameters were calculated with WinNonlin 6.4 software.The statistical analysis was carried with SPSS software.Results The linear calibration curve of leuprolide in canine serum was linear in the range of 0.0781-50.0μg·L^(-1).The main pharmacokinetic parameters after subcutaneous injection of leuprolide acetate sustained-release microspheres were as follows:ρ_(max)(6.01±1.37)μg·L^(-1)and(75.50±11.65)μg·L^(-1),tmax(0.84±0.13)h and(1.31±0.59)h,t_(1/2)(242.62±164.59)h and(388.64±135.75)h,AUC_(0-t)(104.26±46.57)μg·h·L^(-1)and(640.57±180.92)μg·h·L^(-1),AUC_(0-∞)(152.18±79.72)μg·h·L^(-1)and(701.21±178.01)μg·h·L^(-1)under the condition of 3.75 mg and 11.25 mg,respectively.Independentt-test was applied for the determination of statistical difference in pharmacokinetic parameters between the two groups of dose correction.There was no significant difference betweentmax,t_(1/2),AUClast and AUC_(0-∞)(P>0.05).Significant differences between the two groups were observed forρ_(max)(P<0.05).Conclusion Theρ_(max)of the 3.75 mg group is significantly lower than that of the 11.25 mg group,and the 3.75 mg group has lower burst release than the 11.25 mg group.And there is no significant difference in theAUC between the 11.25 mg and the 3.75 mg groups.

关 键 词：亮丙瑞林 药代动力学 犬血清 LC-MS/MS 

分 类 号：R917[医药卫生—药物分析学]